CalciMedica Announces Publication of Preclinical Data in Journal of Clinical Investigation (JCI) Insight Supporting the Development of CRAC Channel Inhibitors for Chronic Pancreatitis (CP)

Results support the initiation of clinical studies to assess Orai1 inhibition in patients with recurrent acute pancreatitis (RAP) and early CP

Data show that inhibiting Orai1-mediated store-operated Ca²⁺ entry (SOCE) with a selective CRAC channel inhibitor prevented the progression of RAP and early CP into established CP

LA JOLLA, Calif., June 06, 2023 (GLOBE NEWSWIRE) -- CalciMedica Inc. (“CalciMedica”) (OTCQB: CALC), a clinical-stage biopharmaceutical company focused on developing therapies for life-threatening inflammatory diseases with high unmet need, today announced the publication of preclinical data in The Journal of Clinical Investigation (JCI) Insight that details the potential benefit of CRAC channel inhibitors for chronic pancreatitis (CP). The study, titled “Orai1 calcium channel inhibition prevents progression of chronic pancreatitis,” was conducted by József Maléth, M.D., Ph.D., and his team at University of Szeged and the manuscript was co-authored by CalciMedica’s co-founder and Chief Scientific Officer, Ken Stauderman, Ph.D., and CalciMedica’s Chief Medical Officer, Sudarshan Hebbar, M.D.

“We are encouraged by the data gathered in this study, which illustrate the potential benefit of Orai1 inhibition with a selective CRAC channel inhibitor for the treatment of chronic pancreatitis,” said Dr. Stauderman. “The data show that inhibition of Orai1 channels diminished aberrant SOCE, restored the expression of SARAF, a protein that inhibits CRAC channels and is decreased in pancreatitis, and prevented the progression of early CP to end-stage disease in mice. In addition, a decrease in fibrosis was observed in the mouse model, consistent with a significant reduction in the severity of CP. The work that we have done with Dr. Maléth and his team builds on previous research with CM5480, a CRAC channel inhibitor tool compound, in acute pancreatitis and suggests that Orai1 inhibition has implications beyond the management of RAP and can act as a treatment for both early and end-stage CP.”

CP is a progressive inflammatory disease characterized by an inability of the SOCE signaling mechanism to properly regulate Ca²⁺ influx, resulting in intracellular Ca²⁺ overload. The study authors aimed to demonstrate that Orai1 inhibition using the selective CRAC channel inhibitor, CM5480, prevents the progression of RAP into early CP, both as simulated by the model, and, eventually, into end-stage CP. The authors found that the use of CM5480 to inhibit Orai1 impaired inflammatory cell infiltration improved acinar cell enzyme activity, maintained ductal cell secretory function and prevented activation of pancreatic stellate cells (PSCs), in turn decreasing tissue damage and fibrosis in CP. As a result, the progression of RAP and early CP into established CP was prevented. These results support the initiation of clinical studies to assess the beneficial effects of Orai1 inhibition in patients with RAP and early CP.